Thrombogenic risk in patients with atrial fibrillation: Importance of comorbid conditions and intracardiac changes

Han S. Lim, Scott R. Willoughby, Carlee Schultz, Muayad Alasady, Geetanjali Rangnekar, Jerry Dang, Cheryl Gan, Dennis H. Lau, Kurt C. Roberts-Thomson, Glenn D. Young, Matthew I. Worthley, Prashanthan Sanders

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives This study sought to determine the differences between the prothrombotic properties and chamber characteristics in patients with lone atrial fibrillation (AF) and those with AF and comorbidities. Background Thromboembolic risk is increased in patients with AF; however, whether this is due to AF per se or its comorbidities remains unclear. Methods A total of 87 patients undergoing ablation were prospectively recruited for the study, including 30 patients with lone AF, 30 patients with AF and comorbidities in sinus rhythm, and 27 patients with left-sided accessory pathways as controls. Blood samples were obtained from the left atrium (LA), right atrium (RA), and femoral vein (FV) after transseptal puncture. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric-dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. Results Platelet activation in the LA was significantly elevated compared to that in the FV in patients with lone AF and those with AF and comorbidities compared with that in the FV (p < 0.05 respectively). Thrombin generation was significantly elevated in the LA compared with RA in AF patients (p < 0.05). There were no significant differences in P-selectin, TAT, and sCD40L among the 3 groups. However, there was a significant stepwise increase in endothelial dysfunction measured by ADMA from controls to lone AF and then to patients with AF and comorbidities (p < 0.001 between the 2 groups). Conclusions Patients with lone AF and those with AF and comorbidities had a greater propensity for atrial thrombogenesis than controls. Prothrombotic risk is greatest in those with comorbid conditions, in whom enhanced thrombogenesis occurs predominantly through increase in endothelial dysfunction.

LanguageEnglish
Pages210-217
Number of pages8
JournalJACC: Clinical Electrophysiology
Volume1
Issue number3
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • atrial fibrillation
  • endothelial dysfunction
  • left atrium
  • stroke prevention
  • thrombotic risk

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Lim, Han S. ; Willoughby, Scott R. ; Schultz, Carlee ; Alasady, Muayad ; Rangnekar, Geetanjali ; Dang, Jerry ; Gan, Cheryl ; Lau, Dennis H. ; Roberts-Thomson, Kurt C. ; Young, Glenn D. ; Worthley, Matthew I. ; Sanders, Prashanthan. / Thrombogenic risk in patients with atrial fibrillation : Importance of comorbid conditions and intracardiac changes. In: JACC: Clinical Electrophysiology. 2015 ; Vol. 1, No. 3. pp. 210-217.
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title = "Thrombogenic risk in patients with atrial fibrillation: Importance of comorbid conditions and intracardiac changes",
abstract = "Objectives This study sought to determine the differences between the prothrombotic properties and chamber characteristics in patients with lone atrial fibrillation (AF) and those with AF and comorbidities. Background Thromboembolic risk is increased in patients with AF; however, whether this is due to AF per se or its comorbidities remains unclear. Methods A total of 87 patients undergoing ablation were prospectively recruited for the study, including 30 patients with lone AF, 30 patients with AF and comorbidities in sinus rhythm, and 27 patients with left-sided accessory pathways as controls. Blood samples were obtained from the left atrium (LA), right atrium (RA), and femoral vein (FV) after transseptal puncture. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric-dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. Results Platelet activation in the LA was significantly elevated compared to that in the FV in patients with lone AF and those with AF and comorbidities compared with that in the FV (p < 0.05 respectively). Thrombin generation was significantly elevated in the LA compared with RA in AF patients (p < 0.05). There were no significant differences in P-selectin, TAT, and sCD40L among the 3 groups. However, there was a significant stepwise increase in endothelial dysfunction measured by ADMA from controls to lone AF and then to patients with AF and comorbidities (p < 0.001 between the 2 groups). Conclusions Patients with lone AF and those with AF and comorbidities had a greater propensity for atrial thrombogenesis than controls. Prothrombotic risk is greatest in those with comorbid conditions, in whom enhanced thrombogenesis occurs predominantly through increase in endothelial dysfunction.",
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author = "Lim, {Han S.} and Willoughby, {Scott R.} and Carlee Schultz and Muayad Alasady and Geetanjali Rangnekar and Jerry Dang and Cheryl Gan and Lau, {Dennis H.} and Roberts-Thomson, {Kurt C.} and Young, {Glenn D.} and Worthley, {Matthew I.} and Prashanthan Sanders",
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Lim, HS, Willoughby, SR, Schultz, C, Alasady, M, Rangnekar, G, Dang, J, Gan, C, Lau, DH, Roberts-Thomson, KC, Young, GD, Worthley, MI & Sanders, P 2015, 'Thrombogenic risk in patients with atrial fibrillation: Importance of comorbid conditions and intracardiac changes', JACC: Clinical Electrophysiology, vol. 1, no. 3, pp. 210-217. https://doi.org/10.1016/j.jacep.2015.03.011

Thrombogenic risk in patients with atrial fibrillation : Importance of comorbid conditions and intracardiac changes. / Lim, Han S.; Willoughby, Scott R.; Schultz, Carlee; Alasady, Muayad; Rangnekar, Geetanjali; Dang, Jerry; Gan, Cheryl; Lau, Dennis H.; Roberts-Thomson, Kurt C.; Young, Glenn D.; Worthley, Matthew I.; Sanders, Prashanthan.

In: JACC: Clinical Electrophysiology, Vol. 1, No. 3, 01.01.2015, p. 210-217.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thrombogenic risk in patients with atrial fibrillation

T2 - JACC: Clinical Electrophysiology

AU - Lim, Han S.

AU - Willoughby, Scott R.

AU - Schultz, Carlee

AU - Alasady, Muayad

AU - Rangnekar, Geetanjali

AU - Dang, Jerry

AU - Gan, Cheryl

AU - Lau, Dennis H.

AU - Roberts-Thomson, Kurt C.

AU - Young, Glenn D.

AU - Worthley, Matthew I.

AU - Sanders, Prashanthan

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Objectives This study sought to determine the differences between the prothrombotic properties and chamber characteristics in patients with lone atrial fibrillation (AF) and those with AF and comorbidities. Background Thromboembolic risk is increased in patients with AF; however, whether this is due to AF per se or its comorbidities remains unclear. Methods A total of 87 patients undergoing ablation were prospectively recruited for the study, including 30 patients with lone AF, 30 patients with AF and comorbidities in sinus rhythm, and 27 patients with left-sided accessory pathways as controls. Blood samples were obtained from the left atrium (LA), right atrium (RA), and femoral vein (FV) after transseptal puncture. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric-dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. Results Platelet activation in the LA was significantly elevated compared to that in the FV in patients with lone AF and those with AF and comorbidities compared with that in the FV (p < 0.05 respectively). Thrombin generation was significantly elevated in the LA compared with RA in AF patients (p < 0.05). There were no significant differences in P-selectin, TAT, and sCD40L among the 3 groups. However, there was a significant stepwise increase in endothelial dysfunction measured by ADMA from controls to lone AF and then to patients with AF and comorbidities (p < 0.001 between the 2 groups). Conclusions Patients with lone AF and those with AF and comorbidities had a greater propensity for atrial thrombogenesis than controls. Prothrombotic risk is greatest in those with comorbid conditions, in whom enhanced thrombogenesis occurs predominantly through increase in endothelial dysfunction.

AB - Objectives This study sought to determine the differences between the prothrombotic properties and chamber characteristics in patients with lone atrial fibrillation (AF) and those with AF and comorbidities. Background Thromboembolic risk is increased in patients with AF; however, whether this is due to AF per se or its comorbidities remains unclear. Methods A total of 87 patients undergoing ablation were prospectively recruited for the study, including 30 patients with lone AF, 30 patients with AF and comorbidities in sinus rhythm, and 27 patients with left-sided accessory pathways as controls. Blood samples were obtained from the left atrium (LA), right atrium (RA), and femoral vein (FV) after transseptal puncture. Platelet activation (P-selectin) was measured by flow cytometry. Thrombin generation (thrombin-antithrombin [TAT] complex), endothelial dysfunction (asymmetric-dimethylarginine [ADMA]), and platelet-derived inflammation (soluble CD40 ligand [sCD40L]) were measured using enzyme-linked immunosorbent assay. Results Platelet activation in the LA was significantly elevated compared to that in the FV in patients with lone AF and those with AF and comorbidities compared with that in the FV (p < 0.05 respectively). Thrombin generation was significantly elevated in the LA compared with RA in AF patients (p < 0.05). There were no significant differences in P-selectin, TAT, and sCD40L among the 3 groups. However, there was a significant stepwise increase in endothelial dysfunction measured by ADMA from controls to lone AF and then to patients with AF and comorbidities (p < 0.001 between the 2 groups). Conclusions Patients with lone AF and those with AF and comorbidities had a greater propensity for atrial thrombogenesis than controls. Prothrombotic risk is greatest in those with comorbid conditions, in whom enhanced thrombogenesis occurs predominantly through increase in endothelial dysfunction.

KW - atrial fibrillation

KW - endothelial dysfunction

KW - left atrium

KW - stroke prevention

KW - thrombotic risk

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U2 - 10.1016/j.jacep.2015.03.011

DO - 10.1016/j.jacep.2015.03.011

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JO - JACC: Clinical Electrophysiology

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SN - 2405-500X

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